Miyar Ata, Habibi Iman, Ebrahimi Ali, Mansourpour Delaram, Mokarizadeh Aram, Rajabi Alireza, Farshgar Rozhin, Eshaghzadeh Mehdi, Zamani-Ahmadmahmudi Mohamad, Nodushan Seyed Mohamad Hossein Tabatabaei
Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
J Neurol Sci. 2016 Sep 15;368:314-7. doi: 10.1016/j.jns.2016.07.046. Epub 2016 Jul 20.
Malignant gliomas are the most common form of primary intracranial tumors with the highest mortality rates. Various gene alterations are considered as prognostic markers in glioma. But, the relevant molecular mechanisms in this setting are not well-understood.
The aim of this study was to assess the association and prognostic value of TLR9 and NFKBIA with clinical significance and also their impact on patient survival in human glioma.
Expression of TLR9 and NFKBIA mRNA in the tissues was determined by immunohistochemistry and qRT-PCR methods. Kaplan-Meier curves and Cox proportional hazards regression model were used to assess the association of TLR9 and NFKBIA with clinical outcomes of patients.
Quantitative real-time PCR analysis showed that TLR9 mRNAs is markedly expressed in glioma tissues than in non-neoplastic tissues (mean±SD: 3.26±0.40 vs. 0.71±0.36, P<0.001). There was also a significant difference between TLR9 mRNAs and high grade glioma (P<0.001).NFKBIA mRNAs was significantly identified in non-neoplastic tissues compared with glioma specimens (mean±SD: 2.76±0.30 vs. 0.94±0.35, P<0.001). Lower levels of NFKBIA mRNA were significantly related to advanced grade of gliomas (P<0.001). Furthermore, Immunoreactivity for high expression of TLR9 was detected in 65% of cases (26/40) that was associated with high grade glioma (P=0.001). No statistically significant correlation was found between TLR9 and other clinical parameters (P>0.05). Immunoreactivity for high expression of NFKBIA was observed in 32.5% (13/40) of cases and NFKBIA expression was decreased in patients with high grad glioma (P=0.014). There was no significant correlation between NFKBIA protein expression and age, sex, and relapse. The Kaplan-Meier analysis indicated that patients with high expression of TLR9 and low expression of NFKBIA are significantly related to poorer OS (P<0.001). In addition, the multivariate Cox regression model revealed that TLR9 and NFKBIA protein expressions (low/high) and tumor grade were potentially an independent predictor of survival in patients (hazard ratio, 2.132, 2.411, 2.13 [95% confidence interval, 1.825-3.782, 1.61-3.231, 1.542-3.92]; P=0.012,P=0.018, P=0.001).
These data indicate that TLR9 and NFKBIA protein expressions act as independent predictor of survival for the diagnosis of glioma and a prognostic biomarker for those with a tumor at an advanced pathological grade.
恶性胶质瘤是最常见的原发性颅内肿瘤形式，死亡率最高。各种基因改变被认为是胶质瘤的预后标志物。但是，在这种情况下相关的分子机制尚未完全了解。
本研究旨在评估Toll样受体9（TLR9）和核因子κB抑制蛋白α（NFKBIA）的相关性、预后价值及其临床意义，以及它们对人类胶质瘤患者生存的影响。
采用免疫组织化学和定量逆转录聚合酶链反应（qRT-PCR）方法检测组织中TLR9和NFKBIA信使核糖核酸（mRNA）的表达。使用Kaplan-Meier曲线和Cox比例风险回归模型评估TLR9和NFKBIA与患者临床结局的相关性。
定量实时PCR分析显示，TLR9 mRNA在胶质瘤组织中的表达明显高于非肿瘤组织（平均值±标准差：3.26±0.40对0.71±0.36，P<0.001）。TLR9 mRNA与高级别胶质瘤之间也存在显著差异（P<0.001）。与胶质瘤标本相比，NFKBIA mRNA在非肿瘤组织中显著表达（平均值±标准差：2.76±0.30对0.94±0.35，P<0.001）。NFKBIA mRNA水平较低与高级别胶质瘤显著相关（P<0.001）。此外，65%（26/40）的病例检测到TLR9高表达的免疫反应性，这与高级别胶质瘤相关（P=0.001）。未发现TLR9与其他临床参数之间存在统计学显著相关性（P>0.05）。32.5%（13/40）的病例观察到NFKBIA高表达的免疫反应性，高级别胶质瘤患者的NFKBIA表达降低（P=0.014）。NFKBIA蛋白表达与年龄、性别和复发之间无显著相关性。Kaplan-Meier分析表明，TLR9高表达和NFKBIA低表达的患者总生存期显著较差（P<目标文本：001）。此外，多变量Cox回归模型显示，TLR9和NFKBIA蛋白表达（低/高）以及肿瘤分级可能是患者生存的独立预测因素（风险比，2.132、2.411、2.13[95%置信区间，1.825-3.782、1.61-3.231、1.542-原文文本：92]；P=0.012、P=0.018、P=0.001）。
这些数据表明，TLR9和NFKBIA蛋白表达可作为胶质瘤诊断的生存独立预测因素，以及病理分级较高的肿瘤患者的预后生物标志物。
